Genome-wide association studies in oesophageal adenocarcinoma and Barrett's oesophagus: a large-scale meta-analysis

Background: Esophageal adenocarcinoma (EA) is one of the fastest rising cancers in western countries. Barrett’s Esophagus (BE) is the premalignant precursor of EA. However, only a subset of BE patients develop EA, which complicates the clinical management in the absence of valid predictors. Genetic risk factors for BE and EA are incompletely understood. This study aimed to identify novel genetic risk factors for BE and EA.Methods: Within an international consortium of groups involved in the genetics of BE/EA, we performed the first meta-analysis of all genome-wide association studies (GWAS) available, involving 6,167 BE patients, 4,112 EA patients, and 17,159 representative controls, all of European ancestry, genotyped on Illumina high-density SNP-arrays, collected from four separate studies within North America, Europe, and Australia. Meta-analysis was conducted using the fixed-effects inverse variance-weighting approach. We used the standard genome-wide significant threshold of 5×10-8 for this study. We also conducted an association analysis following reweighting of loci using an approach that investigates annotation enrichment among the genome-wide significant loci. The entire GWAS-data set was also analyzed using bioinformatics approaches including functional annotation databases as well as gene-based and pathway-based methods in order to identify pathophysiologically relevant cellular pathways.Findings: We identified eight new associated risk loci for BE and EA, within or near the CFTR (rs17451754, P=4·8×10-10), MSRA (rs17749155, P=5·2×10-10), BLK (rs10108511, P=2·1×10-9), KHDRBS2 (rs62423175, P=3·0×10-9), TPPP/CEP72 (rs9918259, P=3·2×10-9), TMOD1 (rs7852462, P=1·5×10-8), SATB2 (rs139606545, P=2·0×10-8), and HTR3C/ABCC5 genes (rs9823696, P=1·6×10-8). A further novel risk locus at LPA (rs12207195, posteriori probability=0·925) was identified after re-weighting using significantly enriched annotations. This study thereby doubled the number of known risk loci. The strongest disease pathways identified (P<10-6) belong to muscle cell differentiation and to mesenchyme development/differentiation, which fit with current pathophysiological BE/EA concepts. To our knowledge, this study identified for the first time an EA-specific association (rs9823696, P=1·6×10-8) near HTR3C/ABCC5 which is independent of BE development (P=0·45).Interpretation: The identified disease loci and pathways reveal new insights into the etiology of BE and EA. Furthermore, the EA-specific association at HTR3C/ABCC5 may constitute a novel genetic marker for the prediction of transition from BE to EA. Mutations in CFTR, one of the new risk loci identified in this study, cause cystic fibrosis (CF), the most common recessive disorder in Europeans. Gastroesophageal reflux (GER) belongs to the phenotypic CF-spectrum and represents the main risk factor for BE/EA. Thus, the CFTR locus may trigger a common GER-mediated pathophysiology.

Evaluating laser-driven Bremsstrahlung radiation sources for imaging and analysis of nuclear waste packages

A small scale sample nuclear waste package, consisting of a 28 mm diameter uranium penny encased in grout, was imaged by absorption contrast radiography using a single pulse exposure from an X-ray source driven by a high-power laser. The Vulcan laser was used to deliver a focused pulse of photons to a tantalum foil, in order to generate a bright burst of highly penetrating X-rays (with energy >500 keV), with a source size of <0.5 mm. BAS-TR and BAS-SR image plates were used for image capture, alongside a newly developed Thalium doped Caesium Iodide scintillator-based detector coupled to CCD chips. The uranium penny was clearly resolved to sub-mm accuracy over a 30 cm2 scan area from a single shot acquisition. In addition, neutron generation was demonstrated in situ with the X-ray beam, with a single shot, thus demonstrating the potential for multi-modal criticality testing of waste materials. This feasibility study successfully demonstrated non-destructive radiography of encapsulated, high density, nuclear material. With recent developments of high-power laser systems, to 10 Hz operation, a laser-driven multi-modal beamline for waste monitoring applications is envisioned.

A state-of-the-art review and feasibility analysis of high altitude wind power in Northern Ireland

In many countries wind energy has become an indispensable part of the electricity generation mix. The opportunity for ground based wind turbine systems are becoming more and more constrained due to limitations on turbine hub heights, blade lengths and location restrictions linked to environmental and permitting issues including special areas of conservation and social acceptance due to the visual and noise impacts. In the last decade there have been numerous proposals to harness high altitude winds, such as tethered kites, airfoils and dirigible based rotors. These technologies are designed to operate above the neutral atmospheric boundary layer of 1,300 m, which are subject to more powerful and persistent winds thus generating much higher electricity capacities. This paper presents an in-depth review of the state-of-the-art of high altitude wind power, evaluates the technical and economic viability of deploying high altitude wind power as a resource in Northern Ireland and identifies the optimal locations through considering wind data and geographical constraints. The key findings show that the total viable area over Northern Ireland for high altitude wind harnessing devices is 5109.6 km2, with an average wind power density of 1,998 W/m2 over a 20-year span, at a fixed altitude of 3,000 m. An initial budget for a 2MW pumping kite device indicated a total cost £1,751,402 thus proving to be economically viable with other conventional wind-harnessing devices.

Energy efficiency in the Chinese provinces: a fixed effects stochastic frontier spatial Durbin error panel analysis

Energy efficiency improvement has been a key objective of China’s long-term energy policy. In this paper, we derive single-factor technical energy efficiency (abbreviated as energy efficiency) in China from multi-factor efficiency estimated by means of a translog production function and a stochastic frontier model on the basis of panel data on 29 Chinese provinces over the period 2003–2011. We find that average energy efficiency has been increasing over the research period and that the provinces with the highest energy efficiency are at the east coast and the ones with the lowest in the west, with an intermediate corridor in between. In the analysis of the determinants of energy efficiency by means of a spatial Durbin error model both factors in the own province and in first-order neighboring provinces are considered. Per capita income in the own province has a positive effect. Furthermore, foreign direct investment and population density in the own province and in neighboring provinces have positive effects, whereas the share of state-owned enterprises in Gross Provincial Product in the own province and in neighboring provinces has negative effects. From the analysis it follows that inflow of foreign direct investment and reform of state-owned enterprises are important policy handles.

Multiscale Analysis for Field-Effect Penetration through Two-Dimensional Materials

Gate-tunable two-dimensional (2D) materials-based quantum capacitors (QCs) and van der Waals heterostructures involve tuning transport or optoelectronic characteristics by the field effect. Recent studies have attributed the observed gate-tunable characteristics to the change of the Fermi level in the first 2D layer adjacent to the dielectrics, whereas the penetration of the field effect through the one-molecule-thick material is often ignored or oversimplified. Here, we present a multiscale theoretical approach that combines first-principles electronic structure calculations and the Poisson–Boltzmann equation methods to model penetration of the field effect through graphene in a metal–oxide–graphene–semiconductor (MOGS) QC, including quantifying the degree of “transparency” for graphene two-dimensional electron gas (2DEG) to an electric displacement field. We find that the space charge density in the semiconductor layer can be modulated by gating in a nonlinear manner, forming an accumulation or inversion layer at the semiconductor/graphene interface. The degree of transparency is determined by the combined effect of graphene quantum capacitance and the semiconductor capacitance, which allows us to predict the ranking for a variety of monolayer 2D materials according to their transparency to an electric displacement field as follows: graphene > silicene > germanene > WS2 > WTe2 > WSe2 > MoS2 > phosphorene > MoSe2 > MoTe2, when the majority carrier is electron. Our findings reveal a general picture of operation modes and design rules for the 2D-materials-based QCs.